tbuckley/cabot-search huggingface dataset:
Symptom Change during Waitlist for Medicated and Nonmedicated Patients with Chronic Depression
Authors: Andreas Høstmælingen, Helene Amundsen Nissen-Lie, Bruce Wampold, Pål G. Ulvenes
Journal: Psychotherapy and Psychosomatics (2023)

Introduction: Patients seeking psychotherapy often spend time on waitlist (WL), the effect of which is largely unknown. WL patients may forego alternative non-psychotherapeutic assistance and thus do more poorly than had they not been placed on a WL. The course of symptoms might also be influenced by use of antidepressant medication (ADM), an issue that remains unexplored in the literature. Objective: In a naturalistic setting, WL symptom change before inpatient psychotherapy (mean weeks of waiting = 22.6) was assessed in a sample (N = 313) of chronically depressed patients. Methods: Using the Beck Depression Inventory-II, patients’ symptoms were tracked at assessment, when admitted to treatment (i.e., after WL), at posttreatment and 1-year follow-up. Multilevel growth curve analysis was used to examine waitlist change for the whole sample as well as for ADM users and nonmedicated patients. Results: Symptoms were reduced significantly from assessment to admittance (Cohen’s d = 0.47). Symptoms reduced less for ADM users (d = 0.39) than for nonmedicated patients (d = 0.65). Conclusion: The findings indicate that chronically depressed patients experience a decrease in symptoms during WL, quite likely due to treatment expectations. We discuss whether less symptom improvement for ADM users could be attributed to iatrogenic comorbidity and a higher degree of demoralization in this group.
<i>EGFR</i>-Mutant NSCLC: Chemo–TKI Bests TKI
Journal: Cancer Discovery (2023)

Findings from FLAURA2, a phase III trial, show that adding chemotherapy to osimertinib, the preferred standard of care for patients with EGFR-mutant non-small cell lung cancer, significantly boosts progression-free survival. Serious side effects are also more likely with the combination, though, so patients should weigh the risk-benefit ratio.
Pregnancy Termination and Postnatal Major Congenital Heart Defect Prevalence After Introduction of Prenatal Cardiac Screening
Authors: Viktor Tomek, Hana Jičínská, Jan Pavlíček, Jan Kovanda, Petr Jehlička, Eva Klásková, Jiří Mrázek, David Čutka, Dagmar Smetanová, Miroslav Břešťák, Pavel Vlašín, Markéta Pavlíková, Václav Chaloupecký, Jan Janoušek, Jan Marek
Journal: JAMA Network Open (2023)

Prenatal cardiac screening of the first and second trimesters has had a major impact on postnatal prevalence of congenital heart defects (CHDs), rates of termination of pregnancy (TOP), and outcomes among children born alive with CHDs.To examine the prenatal and postnatal incidence of major CHDs (ie, necessitating intervention within the first year of life), detection rate trends, rates of TOP, and the association of cardiac screening with postnatal outcomes.In this cross-sectional study, 3827 fetuses with antenatally diagnosed major CHDs in the Czech Republic (population 10.7 million) between 1991 and 2021 were prospectively evaluated with known outcomes and associated comorbidities. Prenatal and postnatal prevalence of CHD in an unselected population was assessed by comparison with a retrospective analysis of all children born alive with major CHDs in the same period (5454 children), using national data registry. Data analysis was conducted from January 1991 to December 2021.Prenatal detection and postnatal prevalence of major CHDs and rate of TOPs in a setting with a centralized health care system over 31 years.A total of 3 300 068 children were born alive during the study period. Major CHD was diagnosed in 3827 fetuses, of whom 1646 (43.0%) were born, 2069 (54.1%) resulted in TOP, and 112 (2.9%) died prenatally. The prenatal detection rate increased from 6.2% in 1991 to 82.8% in 2021 (P < .001). Termination of pregnancy decreased from 70% in 1991 to 43% (P < .001) in 2021. Of 627 fetuses diagnosed in the first trimester (introduced in 2007), 460 were terminated (73.3%). Since 2007, of 2066 fetuses diagnosed in the second trimester, 880 (42.6%) were terminated, resulting in an odds ratio of 3.6 (95% CI, 2.8-4.6; P < .001) for TOP in the first trimester compared with the second trimester. Postnatal prevalence of major CHDs declined from 0.21% to 0.14% (P < .001). The total incidence (combining prenatal detection of terminated fetuses with postnatal prevalence) of major CHD remained at 0.23% during the study period.In this cross-sectional study, the total incidence of major CHD did not change significantly during the 31-year study period. The prenatal detection of major CHD approached 83% in the current era. Postnatal prevalence of major CHD decreased significantly due to early TOPs and intrauterine deaths. The introduction of first trimester screening resulted in a higher termination rate in the first trimester but did not revert the overall decreasing trend of termination for CHDs in general.
Preclinical pediatric brain tumor models for immunotherapy: Hurdles and a way forward
Authors: Deepak Kumar Mishra, Dean Popovski, Shelli M Morris, Andrew Bondoc, Shiva Senthil Kumar, Emily J Girard, James Rutka, Maryam Fouladi, Annie Huang, James M Olson, Rachid Drissi
Journal: Neuro-Oncology (2023)

Brain tumors are the most common solid tumor in children and the leading cause of cancer-related deaths. Over the last few years, improvements have been made in the diagnosis and treatment of children with Central Nervous System tumors. Unfortunately, for many patients with high-grade tumors, the overall prognosis remains poor. Lower survival rates are partly attributed to the lack of efficacious therapies. The advent and success of immune checkpoint inhibitors (ICIs) in adults have sparked interest in investigating the utility of these therapies alone or in combination with other drug treatments in pediatric patients. However, to achieve improved clinical outcomes, the establishment and selection of relevant and robust preclinical pediatric high-grade brain tumor models is imperative. Here, we review the information that influenced our model selection as we embarked on an international collaborative study to test ICIs in combination with epigenetic modifying agents to enhance adaptive immunity to treat pediatric brain tumors. We also share challenges that we faced and potential solutions.
Combined Digital Interventions for Pain Reduction in Patients Undergoing Knee Replacement
Authors: Vicky Duong, Sarah R. Robbins, Simone Dennis, Venkatesha Venkatesha, Manuela L. Ferreira, David J. Hunter
Journal: JAMA Network Open (2023)

Digital technology represents an opportunity to improve outcomes following total knee replacement (TKR). Digitally delivered interventions have been shown to be similar to face-to-face interventions and to increase participation levels in people with osteoarthritis.To assess the effect of a digital technology package in reducing pain compared with usual care following TKR.This randomized clinical trial recruited 102 adults after they received TKR in 3 rehabilitation hospitals in Sydney, Australia, between June 2020 and July 2021.All participants underwent usual care. In addition to usual care, 51 participants received a digital technology package consisting of an exercise app, fitness tracker, and online health coaching. In the usual care group, 51 participants received a fitness tracker but with all notifications turned off and goals for step count, sleep, and active hours removed. Participants were followed up for 12 months (June 2021 to July 2022).The primary outcome was mean knee pain during the past week assessed using a numerical rating scale (range, 0-10, with 10 indicating worst possible pain) at 3 months. In unadjusted analyses, considered primary and based on multiple imputations, independent t tests were used to compare means between groups. Secondary outcomes, including measures of function, activity participation, and quality of life, were analyzed using a generalized estimating equation model that accounted for repeated measurements.Of 102 participants (mean [SD] age, 67.9 [7.2] years; 68 [67%] female; and 92 [90%] White) randomly assigned to intervention or usual care groups, 47 (92%) in each group completed the 3-month follow up. At 3 months, participants in the intervention group demonstrated small but not clinically meaningful improvements in pain compared with the usual care group in the unadjusted intention-to-treat analysis (mean difference, -0.84; 95% CI, -1.59 to -0.10; P = .03). Secondary outcomes indicated a statistically significant reduction in pain intensity, (mean difference, -0.94; 95% CI, -1.82 to -0.06), pain disability (mean difference, -5.42; 95% CI, -10.00 to -0.83), and sedentary behavior (mean difference, -9.76; 95% CI, -19.17 to -0.34) favoring the intervention from baseline to 3, 6, and 12 months.In this randomized clinical trial, a combined digital technology program provided small but not clinically meaningful improvements in pain at 3 months and other longer-term favorable outcomes following TKR compared with usual care. Future studies should tailor digital interventions based on participants' abilities and preferences to ensure that the intervention is appropriate and fosters long-term self-management.Anzctr.org.au Identifier: ACTRN12618001448235.
Travel Time and Distance and Participation in Precision Oncology Trials at the National Cancer Center Hospital
Authors: Yuji Uehara, Takafumi Koyama, Yuki Katsuya, Jun Sato, Kazuki Sudo, Shunsuke Kondo, Tatsuya Yoshida, Hirokazu Shoji, Tatsunori Shimoi, Kan Yonemori, Noboru Yamamoto
Journal: JAMA Network Open (2023)

Genotype-matched trials, which are becoming increasingly important in the precision oncology era, require referrals from institutions providing comprehensive genomic profiling (CGP) testing to those conducting these trials, and the travel burden for trial participation is significant. However, it remains unknown whether travel time or distance are associated with genotype-matched trial participation.To assess whether travel time or distance are associated with disparities in genotype-matched trial participation following CGP testing.This retrospective cohort study from June 2020 to June 2022 included patients with advanced or metastatic solid tumors referred to the National Cancer Center Hospital for participation in genotype-matched trials following CGP testing and discussion by molecular tumor boards. Data were analyzed from June to October 2022.Travel time and distance.The primary and secondary outcomes were enrollment in genotype-matched trials and all-cancer clinical trials, respectively.Of 1127 patients (mean [range] age, 62 [16-85] years; 584 women [52%]; all residents of Japan), 127 (11%) and 241 (21%) were enrolled in genotype-matched trials and all-cancer clinical trials, respectively. The overall median (IQR) travel distance and time were 38 (21-107) km and 55 (35-110) minutes, respectively. On multivariable regression with 23 covariates, travel distance (≥100 km vs <100 km) was not associated with the likelihood of genotype-matched trial participation (26 of 310 patients [8%] vs 101 of 807 patients [12%]; odds ratio [OR], 0.64; 95% CI, 0.40-1.02), whereas in patients with travel time of 120 minutes or more, the likelihood of genotype-matched trial participation was significantly lower than those with travel time less than 120 minutes (19 of 276 patients [7%] vs 108 of 851 patients [13%]; OR, 0.51; 95% CI, 0.29-0.84). The likelihood of genotype-matched trial participation decreased as travel time increased from less than 40 (38 of 283 patients [13%]) to 40 to 120 (70 of 568 patients [12%]) and 120 or more (19 of 276 patients [7%]) minutes (OR, 0.74; 95% CI, 0.48-1.17; OR, 0.41; 95% CI, 0.22-0.74, respectively). Neither travel time nor distance were associated with the likelihood of all-cancer clinical trial participation.In this cohort study of patients undergoing CGP testing, an increased travel time was associated with a decreased likelihood of genotype-matched trial participation. This warrants further research on interventions, such as decentralization of clinical trials to mitigate travel burden.
Prostate cancer screening in African American men: a review of the evidence
Authors: Kevin H Kensler, Roman Johnson, Faith Morley, Mohamed Albrair, Barbra A Dickerman, Roman Gulati, Sarah K Holt, Hari S Iyer, Adam S Kibel, Jenney R Lee, Mark A Preston, Jason L Vassy, Erika M Wolff, Yaw A Nyame, Ruth Etzioni, Timothy R Rebbeck
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Prostate cancer is the most diagnosed cancer in African American men, yet prostate cancer screening regimens in this group are poorly guided by existing evidence, given underrepresentation of African American men in prostate cancer screening trials. It is critical to optimize prostate cancer screening and early detection in this high-risk group because underdiagnosis may lead to later-stage cancers at diagnosis and higher mortality while overdiagnosis may lead to unnecessary treatment. Methods We performed a review of the literature related to prostate cancer screening and early detection specific to African American men to summarize the existing evidence available to guide health-care practice. Results Limited evidence from observational and modeling studies suggests that African American men should be screened for prostate cancer. Consideration should be given to initiating screening of African American men at younger ages (eg, 45-50 years) and at more frequent intervals relative to other racial groups in the United States. Screening intervals can be optimized by using a baseline prostate-specific antigen measurement in midlife. Finally, no evidence has indicated that African American men would benefit from screening beyond 75 years of age; in fact, this group may experience higher rates of overdiagnosis at older ages. Conclusions The evidence base for prostate cancer screening in African American men is limited by the lack of large, randomized studies. Our literature search supported the need for African American men to be screened for prostate cancer, for initiating screening at younger ages (45-50 years), and perhaps screening at more frequent intervals relative to men of other racial groups in the United States.
Glycoprotein Injectable Hydrogels Promote Accelerated Bone Regeneration through Angiogenesis and Innervation
Authors: Debyashreeta Barik, Sharmistha Shyamal, Kapilash Das, Sarita Jena, Mamoni Dash
Journal: Advanced Healthcare Materials (2023)

Glycoproteins are gaining prominence as multifunctional biomaterials. The study reports development of glycoprotein mucin as biomaterial promoting bone regeneration. Mucin 1 deletion has resulted in stiffer femoral bones with scarce presence of osteoblasts in trabecular linings and its role has been established in determining bone mass and mineralization. Limited information about its structure limits its processability, exploration as biomaterial, which is discussed in this study. The role of mucin in ECM (extracellular cellular matrix) formation validated by RNA sequencing analysis of human bone marrow derived mesenchymal stem cells is reported. The structure and stability of mucins is dependent on the presence of glycans in its structure. A thermosensitive hydrogel acquired from thermosensitive Poly (N-isopropyl acrylamide)-(PNIPAM) modified mucin and collagen is developed. The hydrogel demonstrates porous structure and mechanical strength. Newly formed bone tissue is observed at 8 weeks post-implantation in the hydrogel treated groups. The formation of blood vessels, nerves, and bone is observed with upregulation of angiopoietin (ANG), neurofilament heavy chain (NF-H), and osteoadherin (OSAD) or osteocalcin (OCN) respectively in rat calvarial defects. The outcome demonstrates that the thermosensitive injectable hydrogel accelerates repair and healing in calvarial bone defects making it a promising biodegradable biomaterial capable of regenerating bone by promoting angiogenesis and innervation.
Racial and Ethnic Disparities in Long-Acting Injectable Antipsychotic Use in a National Sample of Medicare Beneficiaries With Schizophrenia
Authors: Pengxiang Li, Carmela Benson, Zhi Geng, Sanghyuk Seo, Charmi Patel, Jalpa A. Doshi
Journal: JAMA Network Open (2023)

This cross-sectional study assesses the racial and ethnic disparities in long-acting injectable antipsychotic use in a national sample of Medicare beneficiaries with schizophrenia.
Fabrication of 3D Printed, Core‐and‐Shell Implants as Controlled Release Systems for Local siRNA Delivery
Authors: Dina B. Mahmoud, Christian Wölk, Michaela Schulz‐Siegmund
Journal: Advanced Healthcare Materials (2023)

The development and clinical translation of small interfering RNA (siRNA) therapies remains challenging owing to their poor pharmacokinetics. 3D printing technology presents a great opportunity to fabricate personalized implants for local and sustained delivery of siRNA. Hydrogels can mimic the mechanical properties of tissues, avoiding the problems associated with rigid implants. Herein, a thermoresponsive composite hydrogel suitable for extrusion 3D-printing is formulated to fabricate controlled-release implants loaded with siRNA-Lipofectamine RNAiMAX complexes. A hydrogel matrix mainly composed of uncharged agarose to protect siRNA from decomplexation is selected. Additionally, pluronic F127 and gelatin are added to improve the printability, degradation, and cell adhesion to the implants. To avoid exposing siRNA to thermal stress during the printing process, a core-and-shell design is set up for the implants in which a core of siRNA-complexes loaded-pluronic F127 is printed without heat and enclosed with a shell comprising the thermoresponsive composite hydrogel. The release profile of siRNA-complexes is envisioned to be controlled by varying the printing patterns. The results reveal that the implants sustain siRNA release for one month. The intactness of the released siRNA-complexes is proven until the eighth day. Furthermore, by changing the printing patterns, the release profiles can be tailored.
Deciphering mechanisms of blaNDM gene transmission between human and animals: a genomics study of bacterial isolates from various sources in China, 2015 to 2017
Authors: Kaichao Chen, Miaomiao Xie, Ning Dong, Edward Wai Chi Chan, Rong Zhang, Sheng Chen
Journal: Eurosurveillance (2023)

BackgroundIn China, the blaNDM gene has been recovered from human bacterial isolates since 2011. After 2014, detections of this gene in animal and food bacterial isolates have increasingly been reported.AimWe aimed to understand how blaNDM-bearing bacteria could spread between humans, animals, and animal-derived food.MethodsA total of 288 non-duplicate Escherichia coli strains, including 130 blaNDM-carrying and 158 blaNDM-negative strains were collected from clinical (humans), food-producing animals (pigs) and food (retail pork) sources between 2015 and 2017. The strains were whole genome sequenced. Core-genome-multilocus-sequence-typing was conducted. To investigate if sequence types (STs) found in human, animal or food samples could have a prior origin in a clinical, animal or food-borne animal reservoir, discriminant analysis of principal components (DAPC) was used. Plasmids bearing blaNDM were characterised.ResultsThe 130 blaNDM-carrying E. coli strains comprised a total of 60 STs, with ST167 (10/51), ST77 (6/33) and ST48 (6/46) being most prevalent in clinical, animal and food sources, respectively. Some ST10 and ST167 strains were respectively found among all three sources sampled, suggesting they might enable transfer of blaNDM between sources. DAPC analysis indicated possible transmissions of ST167 from humans to animals and ST10 from animals to human. In 114 of 130 blaNDM-carrying isolates, blaNDM was located on an IncX3 plasmid.ConclusionThis study in a Chinese context suggests that cross-species transmission of certain STs of E. coli harbouring blaNDM on mobile elements, may facilitate the spread of carbapenem-resistant Enterobacteriaceae. Stringent monitoring of blaNDM-bearing E. coli in ecosystems is important.
Practical algorithms for early diagnosis of heart failure and heart stress using <scp>NT‐proBNP</scp>: A clinical consensus statement from the Heart Failure Association of the <scp>ESC</scp>
Authors: Antoni Bayes‐Genis, Kieran F. Docherty, Mark C. Petrie, James L. Januzzi, Christian Mueller, Lisa Anderson, Biykem Bozkurt, Javed Butler, Ovidiu Chioncel, John G.F. Cleland, Ruxandra Christodorescu, Stefano Del Prato, Finn Gustafsson, Carolyn S.P. Lam, Brenda Moura, Rodica Pop‐Busui, Petar Seferovic, Maurizio Volterrani, Muthiah Vaduganathan, Marco Metra, Giuseppe Rosano
Journal: European Journal of Heart Failure (2023)
Receipt of BNT162b2 Vaccine and COVID-19 Ambulatory Visits in US Children Younger Than 5 Years
Authors: Sara Y. Tartof, Timothy B. Frankland, Jeff M. Slezak, Laura Puzniak, Bradley K. Ackerson, Luis Jodar, John M. McLaughlin
Journal: JAMA (2023)

This study examines the association of the receipt of wild-type BNT162b2 vaccine with medically attended COVID-19 outcomes among children younger than 5 years in the US.
Benmelstobart Ups ES-SCLC Survival
Journal: Cancer Discovery (2023)

The combination of the PD-L1 inhibitor benmelstobart, the angiogenesis inhibitor anlotinib, and the chemotherapies etoposide and carboplatin significantly improved progression-free survival and overall survival compared with the chemotherapies alone in patients with newly diagnosed extensive-stage small cell lung cancer. Both survival measures were longer than those seen with any other trials in this population of patients.
Disruption of the microbiota-gut-brain axis is a defining characteristic of the α-Gal A (-/0) mouse model of Fabry disease
Authors: C. Delprete, R. Rimondini Giorgini, E. Lucarini, T.F.S. Bastiaanssen, D. Scicchitano, N. Interino, F. Formaggio, F. Uhlig, C. Ghelardini, N.P. Hyland, J.F. Cryan, R. Liguori, M. Candela, J. Fiori, S. Turroni, L. Di Cesare Mannelli, M. Caprini
Journal: Gut Microbes (2023)

Fabry disease (FD) is an X-linked metabolic disease caused by a deficiency in α-galactosidase A (α-Gal A) activity. This causes accumulation of glycosphingolipids, especially globotriaosylceramide (Gb3), in different cells and organs. Neuropathic pain and gastrointestinal (GI) symptoms, such as abdominal pain, nausea, diarrhea, constipation, and early satiety, are the most frequent symptoms reported by FD patients and severely affect their quality of life. It is generally accepted that Gb3 and lyso-Gb3 are involved in the symptoms; nevertheless, the origin of these symptoms is complex and multifactorial, and the exact mechanisms of pathogenesis are still poorly understood. Here, we used a murine model of FD, the male α-Gal A (-/0) mouse, to characterize functionality, behavior, and microbiota in an attempt to elucidate the microbiota-gut-brain axis at three different ages. We provided evidence of a diarrhea-like phenotype and visceral hypersensitivity in our FD model together with reduced locomotor activity and anxiety-like behavior. We also showed for the first time that symptomology was associated with early compositional and functional dysbiosis of the gut microbiota, paralleled by alterations in fecal short-chain fatty acid levels, which partly persisted with advancing age. Interestingly, most of the dysbiotic features suggested a disruption of gut homeostasis, possibly contributing to accelerated intestinal transit, visceral hypersensitivity, and impaired communication along the gut-brain axis.